Von Recklinghausen neurofibromatosis (NF) has an incidence rate of approximately 1 in 3,000 to 1 in 7,000 births. In spite of this high incidence rate and the extensive clinical experience with NF, little is known about the etiology, early patterns of development, or the reasons for malignant transformation of associated tumors in this disease. An understanding of the variability in expression and rates of progression of the disease has been particularly elusive. The range of lesions encountered in the neurofibromatosis-like disease affectig bicolor damselfish (Pomacentrus partitus) make this an excellent model system for the study of many aspects of the pathogenesis of NF in man. Damselfish neurofibromatosis (DNF) consists of multicentric, disseminated peripheral nerve sheath tumors, including plexiform neurofibromas, malignant schwannomas, and pigmented nerve sheath tumorsTbus, further investigation of the pathogenesis of DNF is warranted 1) Ultrastructural and immunohistochemical techniques will be used to identify the cell types participating in the tumors of DNF. The availability of peripheral nerves in early stages of neoplastic transformation in these fish provides a unique opportunity to examine the characteristics of transforming Schwann cells and their surrounding environment. 2) We will characterize the inflammatory infiltrates in these tumors in order to evaluate their role in determinig the composition and growth rate of neurofibromas. Such interactions may be useful as a model of mast cell effects on tumors in NF. 3) The role of changes in immunocompetence of fish in determinig rates of progression of DNF will be investigated. We will also asses the immune system responses to these tumors using graft rejection assays and mixed leukocyte/tumor cell cultures. 4) Our data have shown that DNF is transmissible in the laboratory and that the mechanism of transmission involves transformation of host nerves and probably does not involve proliferation of transplanted tumor cells. These findings suggest the possibility of a viral etiology for DNF. The necessary and sufficient conditions for transmission of these tumors will be evaluated. Subcellular fractions of tumor tissue will be isolated and assessed for tumorigenicity and potential content of viral particles using in vivo and in vitro assay techniques. Relative differences in expression of cellular oncogenes between normal and tumor tissue will be evaluated using standard Northern blot hybridization techniques.